Concomitant Opioid and Diazepam Use in Plastic Surgery

Sir,

The opioid epidemic in the United States continues to accelerate, with 42,000 deaths in 2016 and preliminary U.S. Centers for Disease Control and Prevention data indicating 72,000 deaths in 2017 due to drug overdose (nearly 200 individuals per day).¹ At least two-thirds of these deaths are secondary to opioids.¹ Of particular concern is the increasing incidence of drug overdose due to concomitant opioid and benzodiazepine use, which results in synergistic respiratory depression that greatly increases the risk of overdose and death.² Between 2001 and 2011, there was a 300% increase in combined opioid–benzodiazepine-related emergency department visits.³ When evaluating prescription refills in the 6 months before a drug-related death, risk was shown to be 3 times higher in patients who had refilled an opioid prescription, 7 times higher in patients who had filled a benzodiazepine, and 15 times higher in patients who had filled both in the last 6 months.⁴ In August 2016, a black box warning for coadministration of these medications was issued due to concern for serious harm to patients.

At the University of Wisconsin–Madison, patients undergoing procedures that are thought to result in significant postoperative pain due to muscle spasm (eg, abdominoplasty, tissue expander-based breast reconstruction) have been receiving concomitant muscle relaxant (most commonly diazepam) and opioid prescriptions for the management of postoperative pain for many years. This practice began before the data demonstrating potential harm with the coadministration of these medications. In light of the opioid epidemic, we have overhauled our perioperative pain management practice guidelines to decrease opioid exposure and change prescribing patterns based on the best available evidence. In investigating the evidence for use of diazepam for muscle spasm, we discovered a paucity of the literature regarding this indication. Only 1 trial has investigated the use of diazepam to reduce muscle spasm, which found no difference from placebo.⁵

To date, no blinded, randomized trial has investigated the role of diazepam in the treatment of postoperative muscle spasm. Moreover, no study has evaluated the safety and efficacy of concomitant postoperative opioid and diazepam use. To improve patient safety while maintaining adequate postoperative pain control, it is critical to understand the risks and benefits of opioid and diazepam use in our patients.

Given this challenge, we are initiating a prospective, double-blinded, randomized controlled trial at our institution to evaluate the safety and efficacy of concomitant diazepam and opioid administration after abdominoplasty. We anticipate improved pain control in patients receiving both opioids and benzodiazepines, consistent with anecdotal reports thus far. However, it is imperative that we affirm the safety of this practice before continuing these prescribing patterns, due to the potential for harm not only in synergistic acute respiratory depression but also for long- term addiction. We urge plastic surgeons to exercise caution, counsel patients, and be cognizant of the risks associated with the concomitant use of diazepam and opioids. Ultimately, we hope to identify the optimal postoperative analgesia regimen that will allow patients to balance comfort with safety.